Immunomodulatory functions of surfactant

1997 ◽  
Vol 77 (4) ◽  
pp. 931-962 ◽  
Author(s):  
J. R. Wright
Keyword(s):  
Immune Cell ◽  
Lung Surfactant ◽  
Carbohydrate Binding ◽  
Cell Functions ◽  
Disease States ◽  
Lipoprotein Complex ◽  
The Subject ◽  
Air Liquid Interface

The possibility that the lipoprotein complex of lung surfactant functions in pulmonary host defense as well as lowering surface tension at the air-liquid interface has been the subject of renewed interest in light of the finding that surfactant proteins A and D (SP-A and SP-D) are members of a family of proteins known as collectins. The collectins, so named because they have in common an NH2-terminal collagen-like domain and a COOH-terminal lectin (carbohydrate binding) domain, are found in both lung and serum and participate in "innate" immunity, acting before induction of an antibody-mediated response. In vitro, many of the collectins stimulate phagocytosis, chemotaxis, and production of reactive oxygen and regulate cytokine release by immune cells. It has been known for several years that surfactant lipids suppress a variety of immune cell functions, most notably lymphocyte proliferation, which, conversely, is augmented by SP-A. Thus surfactant lipids and proteins may be counterregulatory, and changes in lipid-to-protein ratios may be important in regulating the immune status of the lung. That these ratios change in disease states is clear, but it is not known whether the alterations are a cause or an effect. Important future studies with mice in which the SP-A and SP-D genes have been ablated will help clarify the role of surfactant in immune function.

scholarly journals Megakaryocytes Display Innate Immune Cell Functions and Respond during Sepsis

2019 ◽  
Author(s):  
Galit H. Frydman ◽  
Felix Ellett ◽  
Julianne Jorgensen ◽  
Anika L. Marand ◽  
Lawrence Zukerberg ◽  
...  
Keyword(s):  
Immune Cell ◽  
Leukemia Cell ◽  
Peripheral Circulation ◽  
Innate Immune ◽  
Innate Immune Cell ◽  
Leukemia Cell Line ◽  
Megakaryoblastic Leukemia ◽  
Cell Functions

AbstractMegakaryocytes (MKs) are precursors to platelets, the second most abundant cells in the peripheral circulation. However, while platelets are known participate in immune responses and play significant roles during infections, the role of MKs within the immune system has not been explored. Here we utilizein vitrotechniques to show that both cord blood-derived MKs (CB MKs) and MKs from a human megakaryoblastic leukemia cell line (Meg-01) chemotax towards pathogenic stimuli, phagocytose bacteria, and release chromatin webs in response to bacteria. Moreover, in patients with sepsis, we found that MK counts were significantly higher in the peripheral blood, and CD61+staining was increased in the kidneys and lungs, correlated with the development of organ dysfunction. Overall, our study suggests that MK cells display basic innate immune cell functions and respond during infections and sepsis.

scholarly journals DDRE-09. DEVELOPING IDO-PROTACS TO IMPROVE IMMUNOTHERAPEUTIC EFFICACY IN PATIENTS WITH GLIOBLASTOMA

2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii63-ii63
Author(s):  
Lakshmi Bollu ◽  
Derek Wainwright ◽  
Lijie Zhai ◽  
Erik Ladomersky ◽  
Kristen Lauing ◽  
...  
Keyword(s):  
Protein Degradation ◽  
Time Course ◽  
Immune Cell ◽  
Enzyme Inhibitors ◽  
Tumor Development ◽  
Ubiquitin Proteasome System ◽  
Degradation Pathway ◽  
Specific Protein ◽  
Cell Functions

Abstract INTRODUCTION Indoleamine 2,3-dioxygenase 1 (IDO; IDO1) is a rate-limiting enzyme that metabolizes the essential amino acid tryptophan into kynurenine. Recent work by our group has revealed that IDO promotes tumor development and suppresses immune cell functions independent of its enzyme activity. Moreover, pharmacologic IDO enzyme inhibitors that currently serve as the only class of drugs available for targeting immunosuppressive IDO activity, fail to improve the survival of patients with GBM. Here, we developed IDO-Proteolysis Targeting Chimeras (IDO-PROTACs). PROTACs bind to a specific protein and recruit an E3 ubiquitin ligase that enhance proteasome-mediated degradation of the target protein. METHODS A library of ≥100 IDO-PROTACs were developed by joining BMS986205 (IDO binder) with a linker group to various E3-ligase ligands. Western blot analysis of PROTAC-induced IDO degradation was tested in vitro among multiple human and mouse GBM cell lines including U87, GBM6, GBM43 and GL261 along a time course ranging between 1–96 hours of treatment and at varying concentrations. The mechanism of IDO protein degradation was investigated using pharmacologic ligands that inhibit or compete with the proteasome-mediated protein degradation pathway. RESULTS Primary screening identified several IDO-PROTACs with IDO protein degradation potential. Secondary screening showed that our lead compound has a DC50 value of ~0.5µM with an ability to degrade IDO in all GBM cells analyzed, and an initial activity within 12 hours of treatment that extended for up to 96 hours. Mutating the CRBN-binding ligand, pretreatment with the ubiquitin proteasome system inhibitors MG132 or MLN4924 or using unmodified parental compound all inhibited IDO protein degradation. CONCLUSIONS This study developed an initial IDO-PROTAC technology that upon further optimization, can neutralize both IDO enzyme and non-enzyme immunosuppressive effects. When combined with other forms of immunotherapy, IDO-PROTACs have the potential to substantially enhance immunotherapeutic efficacy in patients with GBM.

scholarly journals Antioxidant Properties of Ergosterol and Its Role in Yeast Resistance to Oxidation

Antioxidants ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1024
Author(s):  
Sebastien Dupont ◽  
Paul Fleurat-Lessard ◽  
Richtier Gonçalves Cruz ◽  
Céline Lafarge ◽  
Cédric Grangeteau ◽  
...  
Keyword(s):  
Computational Study ◽  
Antioxidant Properties ◽  
Beneficial Effects ◽  
Tert Butyl Hydroperoxide ◽  
Resistance To Oxidation ◽  
Specific Accumulation ◽  
The Subject

Although the functions and structural roles of sterols have been the subject of numerous studies, the reasons for the diversity of sterols in the different eukaryotic kingdoms remain unclear. It is thought that the specificity of sterols is linked to unidentified supplementary functions that could enable organisms to be better adapted to their environment. Ergosterol is accumulated by late branching fungi that encounter oxidative perturbations in their interfacial habitats. Here, we investigated the antioxidant properties of ergosterol using in vivo, in vitro, and in silico approaches. The results showed that ergosterol is involved in yeast resistance to tert-butyl hydroperoxide and protects lipids against oxidation in liposomes. A computational study based on quantum chemistry revealed that this protection could be related to its antioxidant properties operating through an electron transfer followed by a proton transfer mechanism. This study demonstrates the antioxidant role of ergosterol and proposes knowledge elements to explain the specific accumulation of this sterol in late branching fungi. Ergosterol, as a natural antioxidant molecule, could also play a role in the incompletely understood beneficial effects of some mushrooms on health.

425 In-vitro regulation of immune cell functions by human IgE

1991 ◽  
Vol 87 (1) ◽  
pp. 246
Author(s):  
R PARHAR ◽  
P ERNST ◽  
F ALMOHANNA ◽  
A KWAASI ◽  
K SHETH ◽  
...  
Keyword(s):  
Immune Cell ◽  
Cell Functions

scholarly journals Resolvins as Regulators of the Immune System

2010 ◽  
Vol 10 ◽  
pp. 818-831 ◽  
Author(s):  
Hiroyuki Seki ◽  
Takaharu Sasaki ◽  
Tomomi Ueda ◽  
Makoto Arita
Keyword(s):  
Immune System ◽  
Acute Inflammation ◽  
Immune Cell ◽  
Inflammatory Responses ◽  
Bioactive Metabolites ◽  
Cell Functions ◽  
First Response ◽  
Beneficial Impact

Inflammation is the first response of the immune system to infection or injury, but excessive or inappropriate inflammatory responses contribute to a range of acute and chronic human diseases. Clinical assessment of dietary supplementation of ω-3 polyunsaturated fatty acids (i.e., eicosapentaenoic acid [EPA] and docosahexaenoic acid [DHA]) indicate that they have beneficial impact on these diseases, although the mechanisms are poorly understood at the molecular level. In this decade, it has been revealed that EPA and DHA are enzymatically converted to bioactive metabolites in the course of acute inflammation and resolution. These metabolites were shown to regulate immune cell functions and to display potent anti-inflammatory actions bothin vitroandin vivo. Because of their ability to resolve an acute inflammatory response, they are referred to as proresolving mediators, or resolvins. In this review, we provide an overview of the formation and actions of these lipid mediators.

scholarly journals Revisiting the role of IRF3 in inflammation and immunity by conditional and specifically targeted gene ablation in mice

2018 ◽  
Vol 115 (20) ◽  
pp. 5253-5258 ◽  
Author(s):  
Hideyuki Yanai ◽  
Shiho Chiba ◽  
Sho Hangai ◽  
Kohei Kometani ◽  
Asuka Inoue ◽  
...  
Keyword(s):  
Immune Cell ◽  
Cell Types ◽  
Type I ◽  
Type I Ifn ◽  
Cell Type ◽  
Gene Ablation ◽  
Cell Type Specific

IFN regulatory factor 3 (IRF3) is a transcription regulator of cellular responses in many cell types that is known to be essential for innate immunity. To confirm IRF3’s broad role in immunity and to more fully discern its role in various cellular subsets, we engineered Irf3-floxed mice to allow for the cell type-specific ablation of Irf3. Analysis of these mice confirmed the general requirement of IRF3 for the evocation of type I IFN responses in vitro and in vivo. Furthermore, immune cell ontogeny and frequencies of immune cell types were unaffected when Irf3 was selectively inactivated in either T cells or B cells in the mice. Interestingly, in a model of lipopolysaccharide-induced septic shock, selective Irf3 deficiency in myeloid cells led to reduced levels of type I IFN in the sera and increased survival of these mice, indicating the myeloid-specific, pathogenic role of the Toll-like receptor 4–IRF3 type I IFN axis in this model of sepsis. Thus, Irf3-floxed mice can serve as useful tool for further exploring the cell type-specific functions of this transcription factor.

scholarly journals Medawar’s PostEra: Galectins Emerged as Key Players During Fetal-Maternal Glycoimmune Adaptation

2021 ◽  
Vol 12 ◽  
Author(s):  
Ellen Menkhorst ◽  
Nandor Gabor Than ◽  
Udo Jeschke ◽  
Gabriela Barrientos ◽  
Laszlo Szereday ◽  
...  
Keyword(s):  
Immune Cell ◽  
Successful Pregnancy ◽  
Fetal Health ◽  
The Past ◽  
Mammalian Embryogenesis ◽  
Carbohydrate Ligands ◽  
Membrane Bound

Lectin-glycan interactions, in particular those mediated by the galectin family, regulate many processes required for a successful pregnancy. Over the past decades, increasing evidence gathered from in vitro and in vivo experiments indicate that members of the galectin family specifically bind to both intracellular and membrane bound carbohydrate ligands regulating angiogenesis, immune-cell adaptations required to tolerate the fetal semi-allograft and mammalian embryogenesis. Therefore, galectins play important roles in fetal development and placentation contributing to maternal and fetal health. This review discusses the expression and role of galectins during the course of pregnancy, with an emphasis on maternal immune adaptions and galectin-glycan interactions uncovered in the recent years. In addition, we summarize the galectin fingerprints associated with pathological gestation with particular focus on preeclampsia.

The Role of Inflammation in Traumatic Brain Injury

Neurotrauma ◽  
2018 ◽  
pp. 211-232
Author(s):  
Sarah C. Hellewell ◽  
Bridgette D. Semple ◽  
Jenna M. Ziebell ◽  
Nicole Bye ◽  
Cristina Morganti-Kossmann
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Glial Cells ◽  
Immune Cell ◽  
Brain Trauma ◽  
Multiple Roles ◽  
Cell Functions ◽  
Macrophage Populations

Inflammation occurring following brain trauma represents a significant constituent of complex secondary responses that dictate patients’ outcome. Although a few decades have passed since its discovery, new aspects of this intriguing phenomenon are still being uncovered, ranging from the multiple roles of mediators regulating the inception, progression, and resolution of neuroinflammation, to the development of antiinflammatory therapies. This review provides a summary of the vast research on traumatic brain injury inflammation. The authors describe the fundamental aspects of cytokine and immune cell functions, the orchestrated collaboration of chemokines and leukocytes, the phenotypic distinction of macrophage populations, and the contribution of glial cells. Among the beneficial properties of neuroinflammation, they briefly discuss cytokines’ impact on neurogenesis; the chapter concludes by touching on the implications of antiinflammatory therapies.

scholarly journals Microbiota-independent immunological effects of non-digestible oligosaccharides in the context of inflammatory bowel diseases

2020 ◽  
Vol 79 (4) ◽  
pp. 468-478 ◽  
Author(s):  
Stefania Del Fabbro ◽  
Philip C. Calder ◽  
Caroline E. Childs
Keyword(s):  
Inflammatory Bowel Diseases ◽  
Immune Cell ◽  
Intestinal Inflammation ◽  
Mechanisms Of Action ◽  
Mucosal Inflammation ◽  
Disease States ◽  
Inflammatory Conditions ◽  
Bowel Diseases ◽  
Inflammatory Bowel

The aim of the present paper is to review the effects of non-digestible oligosaccharides (NDO) on immunity, focusing on their microbiota-independent mechanisms of action, as well as to explore their potential beneficial role in inflammatory bowel diseases (IBD). IBD are chronic, inflammatory conditions of the gastrointestinal tract. Individuals with IBD have an aberrant immune response to commensal microbiota, resulting in extensive mucosal inflammation and increased intestinal permeability. NDO are prebiotic fibres well known for their role in supporting intestinal health through modulation of the gut microbiota. NDO reach the colon intact and are fermented by commensal bacteria, resulting in the production of SCFA with immunomodulatory properties. In disease states characterised by increased gut permeability, prebiotics may also bypass the gut barrier and directly interact with intestinal and systemic immune cells, as demonstrated in patients with IBD and in infants with an immature gut. In vitro models show that fructooligosaccharides, inulin and galactooligosaccharides exert microbiota-independent effects on immunity by binding to toll-like receptors on monocytes, macrophages and intestinal epithelial cells and by modulating cytokine production and immune cell maturation. Moreover, animal models and human supplementation studies demonstrate that some prebiotics, including inulin and lactulose, might reduce intestinal inflammation and IBD symptoms. Although there are convincing preliminary data to support NDO as immunomodulators in the management of IBD, their mechanisms of action are still unclear and larger standardised studies need to be performed using a wider range of prebiotics.

scholarly journals The Immune Endocannabinoid System of the Tumor Microenvironment

2020 ◽  
Vol 21 (23) ◽  
pp. 8929
Author(s):  
Melanie Kienzl ◽  
Julia Kargl ◽  
Rudolf Schicho
Keyword(s):  
Tumor Microenvironment ◽  
Tumor Progression ◽  
Immune Cells ◽  
Cannabinoid Receptors ◽  
Immune Cell ◽  
Tumor Development ◽  
Endocannabinoid System ◽  
Cell Functions ◽  
In Vitro Effects

Leukocytes are part of the tumor microenvironment (TME) and are critical determinants of tumor progression. Because of the immunoregulatory properties of cannabinoids, the endocannabinoid system (ECS) may have an important role in shaping the TME. Members of the ECS, an entity that consists of cannabinoid receptors, endocannabinoids and their synthesizing/degrading enzymes, have been associated with both tumor growth and rejection. Immune cells express cannabinoid receptors and produce endocannabinoids, thereby forming an “immune endocannabinoid system”. Although in vitro effects of exogenous cannabinoids on immune cells are well described, the role of the ECS in the TME, and hence in tumor development and immunotherapy, is still elusive. This review/opinion discusses the possibility that the “immune endocannabinoid system” can fundamentally influence tumor progression. The widespread influence of cannabinoids on immune cell functions makes the members of the ECS an interesting target that could support immunotherapy.

Sign in / Sign up

Export Citation Format

Share Document